Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder

Efficacy and Safety of Toludesvenlafaxine Hydrochloride Sustained-release Tablets Versus Venlafaxine Hydrochloride Sustained-release Tablets in Patients With Major Depression Disorder: a Multicentre, Open-label, Parallel-group, Randomised Controlled Trial

The purpose of this study is to evaluate efficacy and safety of toludesvenlafaxine hydrochloride sustained-release tablets in the treatment of major depression disorder compared to venlafaxine hydrochloride sustained-release tablets, to provide evidence-based basis for clinical rational drug use.

Study Overview

• Status: Completed
• Conditions: Major Depression Disorder
• Intervention / Treatment: Drug: Toludesvenlafaxine hydrochloride sustained-release tablets; Drug: Venlafaxine hydrochloride sustained-release tablets

Detailed Description

The study included 80 patients with major depression disorder (aged 18 to 65 years) who meet the diagnostic criteria for depression in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Eligible patients were randomly assigned (1:1) to 8-week treatment with toludesvenlafaxine hydrochloride sustained-release tablets (n=40) or venlafaxine hydrochloride sustained-release tablets (n=40), followed up at period of enrollment as baseline and at the end of 2th, 4th and 8th weeks. Adverse events were recorded.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The first Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects meet the diagnostic criteria for major depression disorder in the Diagnostic and Statistical Manual of Manual Disorders, fifth Edition (DSM-5);
• Male or female aged ≥18 and ≤65 years;
• Subjects who have a 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≥18 points;
• Subjects who have a total score of Snaith-Hamilton Pleasure Scale (SHARPS) ≥3 points;
• Subjects voluntarily participate in the study and sign the informed consent form.

Exclusion Criteria:

• Allergic or known to be allergic to toludesvenlafaxine hydrochloride sustained-release tablets and venlafaxine hydrochloride sustained-release tablets;
• Subjects have a severe self-injury/clear suicide attempt or behavior; Scores on HAM-D17 items factor 3 ≥3 points;
• Subjects who meet the diagnostic criteria for any other psychotic disorders in DSM-5;
• Subjects who meet the diagnostic criteria for substance disorders or alcohol abuse in DSM-5 (except for nicotine or caffeine) within the past six months;
• Individuals with severe and unstable physical diseases such as cardiovascular disease, liver disease, kidney disease, blood disorders, and endocrine disorders;
• Hypertensive patients with poor blood pressure control (systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg at screening);
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 2 times / creatinine (Cr) 1.2 times higher than the upper limit of normal at screening;
• Electrocardiogram (ECG) abnormalities that are clinically significant at period of screening and that the investigator considers as inappropriate conditions for inclusion, such as QTc interval >450 ms in men and QTc interval >460 ms in female;
• Subjects who received electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within 3 months prior to screening;
• Subjects who received systematic psychotherapy (interpersonal relationship therapy, dynamic therapy, cognitive behavioral therapy) within 3 months prior to screening;
• Pregnant or lactating women, recent planned pregnancy and unable to ensure effective contraception during the period;
• Other conditions that the investigator considers the participant is not suitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toludesvenlafaxine hydrochloride sustained-release tablets treatment group	Drug: Toludesvenlafaxine hydrochloride sustained-release tablets; 80 mg or 120 mg or 160 mg orally once daily dosing for 8 weeks
Active Comparator: Venlafaxine hydrochloride sustained-release tablets treatment group	Drug: Venlafaxine hydrochloride sustained-release tablets; 75 mg or 150 mg or 225 mg orally once daily dosing for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Snaith-Hamilton Pleasure Scale (SHAPS) Total Score	The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Each item is rated as either 0 or 1, for a total score between 0 and 14, with higher scores corresponding to higher levels of anhedonia.	Baseline and the end of week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dimensional Anhedonia Rating Scale (DARS) Score	DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in major depressive disorder (MDD), and particularly to increase scale generalizability while maintaining specificity. Respondents provide their own examples of rewarding experiences across the domains of hobbies, social activities, food/drink, and sensory experience. Participants answer a set of standardized questions about desire, motivation, effort, and consummatory pleasure with a recall period of "right now" for the examples provided. The instrument is scored as a total sum of all items (range 0-68) with higher scores reflecting increased motivation, effort and pleasure (that is, less anhedonia).	Baseline, the end of Week 2, 4 and 8
Montgomery-Asberg Depression Rating Scale (MADRS) Score	The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.	Baseline, the end of Week 2, 4 and 8
17-item Hamilton Depression Rating Scale (HAM-D17) Score	HAM-D17 has been the gold standard for the assessment of depression. The score needs to be based on clinical interviews, and the time frame of the assessment is usually the situation in the previous week. Most items use a 5-point scale of 0 to 4. The standard of each level is: 0 indicates none, 1 indicates mild, 2 indicates moderate, 3 indicates severe, and 4 indicates extremely severe. A few items adopt the 3-level scoring method with 0~2 points, and the grading standard is: 0 indicates none, 1 indicates mild to moderate and 2 indicates severe.	Baseline, the end of Week 2, 4 and 8
Sheehan Disability Scale (SDS) Score	SDS is composed of three self-rating dimensions, which assess functional status in work, social life/leisure activities, and family life/family responsibilities. Each dimension is scored on a scale of 0 to 10, with 1 to 3 indicating mild impairment, 4 to 6 indicating moderate impairment, 7 to 9 indicating significant impairment, and 10 indicating extreme severity. The three dimensions can also be added together to reflect the overall functional deficiency. The score ranges from 0 to 30, with 0 indicating no damage and 30 indicating significant damage.	Baseline, the end of Week 2, 4 and 8
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) Score	Q-LES-Q-SF consists of 16 self-rated items. Each item is divided into five grades: 1 indicates very dissatisfied, 2 indicates dissatisfied, 3 indicates average, 4 indicates satisfied, and 5 indicates very satisfied. The higher the score, the better the happiness and quality of life satisfaction of the subjects. The first 14 items are used to generate an overall score, while the remaining 2 items are individual items that measure satisfaction and overall quality of life related to the study drug.	Baseline, the end of Week 2, 4 and 8
Snaith-Hamilton Pleasure Scale (SHAPS) Total Score	The SHAPS is a well-validated 14-item self-report questionnaire commonly used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater pleasure capacity. A total score can be derived by summing the responses to each item. Each item is rated as either 0 or 1, for a total score between 0 and 14, with higher scores corresponding to higher levels of anhedonia.	Baseline, the end of Week 2 and 4
Snaith-Hamilton Pleasure Scale (SHAPS) Reductive Rate	Snaith-Hamilton Pleasure Scale (SHAPS) Reductive Rate(%) = (pre-treatment score - post-treatment score)/pre-treatment score ×100%. SHAPS Reductive Rate(%) ≥75% is recovery, 50% ~ 74% is significantly effective, 25% ~ 49% is effective, and < 25% is ineffective.	The end of Week 2, 4 and 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arizona Sexual Experience Scale (ASEX) Score	ASEX is designed to assess aspects of psychotropic drug-induced sexual dysfunction: drive, arousal, penile erection/vaginal lubrication, ability to reach orgasm, and satisfaction from orgasm. The ASEX can be self- or clinician-administered. The 5 questions are rated using 6-point Likert-type scales with varying endpoints. Possible total scores range from 5 to 30, with the higher scores indicating more sexual dysfunction.	Baseline, the end of Week 2, 4 and 8
Count of red blood cell in blood	To analysis whether count of red blood cell in blood show any significant trend with time changes.	Baseline, the end of Week 8
Count of white blood cell in blood	To analysis whether count of white blood cell in blood show any significant trend with time changes.	Baseline, the end of Week 8
Count of platelet in blood	To analysis whether count of platelet in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of hemoglobin in blood	To analysis whether concentration of hemoglobin in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of alanine aminotransferase in blood	To analysis whether concentration of alanine aminotransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of aspartate aminotransferase in blood	To analysis whether concentration of aspartate aminotransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of gamma-glutamyltransferase in blood	To analysis whether concentration of gamma-glutamyltransferase in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of blood glucose in blood	To analysis whether concentration of blood glucose in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of serum creatinine in blood	To analysis whether concentration of serum creatinine in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of urea in blood	To analysis whether concentration of urea in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of total cholesterol in blood	To analysis whether concentration of total cholesterol in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of high density lipoprotein in blood	To analysis whether concentration of high density lipoprotein in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of low density lipoprotein in blood	To analysis whether concentration of low density lipoprotein in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of triglyceride in blood	To analysis whether concentration of triglyceride in blood show any significant trend with time changes.	Baseline, the end of Week 8
Concentration of protein in urine	To analysis whether concentration of protein in urine show any significant trend with time changes.	Baseline, the end of Week 8
Count of white blood cell in urine	To analysis whether count of white blood cell in urine show any significant trend with time changes.	Baseline, the end of Week 8
Count of red blood cell in urine	To analysis whether count of red blood cell in urine show any significant trend with time changes.	Baseline, the end of Week 8
ECG QT Interval	To analysis whether ECG QT Interval of participants show any significant trend with time changes.	Baseline, the end of Week 8
Changes in weight	To analysis whether weight of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in pulse	To analysis whether pulse of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in both systolic and diastolic blood pressure	To analysis whether blood pressure including systolic blood pressure and diastolic blood pressure of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in respiration rate	To analysis whether respiration rate of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Changes in armpit temperature	To analysis whether armpit temperature of participants show any significant trend with time changes.	Baseline, the end of Week 2, 4 and 8
Concentration of sugar in urine	To analysis whether concentration of sugar in urine show any significant trend with time changes.	Baseline, the end of Week 8
Treatment Emergent Symptom Scale (TESS) Score	Treatment Emergent Symptom Scale was developed by The National Institute of Mental Health (NIMH) in the USA in 1973. It is a safety assessment tool after treatment of psychiatric diseases. Evaluation is based on patient reports, physical examination results, and laboratory reports, and some items should also be consulted with the patient's family. Severity item is scored from 0 (not present) to 4 (severe). Higher scores represent a more severe condition.	The end of Week 2, 4 and 8

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Actual): November 10, 2024
• Study Completion (Actual): November 19, 2024

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: February 18, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 27, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Serotonin and Noradrenaline Reuptake Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Antidepressive Agents; Antidepressive Agents, Second-Generation; Venlafaxine Hydrochloride
• Other Study ID Numbers: RXL-RCT-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No